Type 1 diabetes (T1D) in pregnancy is associated with considerably increased rates of adverse obstetric and neonatal outcomes. Nationwide studies confirm a two- to five-fold increased risk of congenital malformation, stillbirth and neonatal death.1-3 At least 50% of pregnancies are complicated by additional obstetric and perinatal complications, including pre-eclampsia, preterm delivery, delivery by caesarean section and large for gestational age (LGA) offspring, with data suggesting that rates of LGA and fetal macrosomia are increasing.3, 7 The importance of avoiding hyperglycaemia to reduce obstetric complications, neonatal morbidity and LGA is well recognised.5, 6 Therefore, to deliver healthy infants, women with T1D are advised to carefully plan their pregnancies, attend structured education/prepregnancy care (PPC) and aim for near-normal blood glucose levels before and during pregnancy.7 However, many pregnancies are unplanned and even the most motivated women attending structured education and PPC struggle to achieve optimal glycaemic control.4, 8 During 2006–2009, only 10% of women with T1D who attended PPC in East Anglia achieved preconception HbA1c levels <6.1% (43mmol/mol). Consequently, despite improved preconception counselling and increased PPC attendance, glycaemic control and pregnancy outcomes remained suboptimal. Technological advances were not routinely available, 90% of women used multiple daily injections (MDI) without continuous glucose monitoring (CGM), and only 10% of women had continuous subcutaneous insulin infusion (CSII) therapy before or during pregnancy. Audit data confirm similarly poor glycaemic control and pregnancy outcomes across the UK.9 Outside pregnancy, there have been unprecedented advances in the technology available for managing T1D, with growing acknowledgement of the potential benefits of CGM, CSII and, most recently, sensor augmented pump (SAP) therapy. Several studies confirm the benefits of regular real-time or personal CGM use (>6 days per week) in achieving tight glycaemic control among children and motivated adults.10-12 However, these studies also highlight the challenges in adolescents (presumed to be less motivated) and limitations of CGM in preventing hypoglycaemia, with frequent and prolonged nocturnal episodes despite regular CGM use.13 A recent health technology assessment concluded that pump therapy offers advantages over MDI: namely, better blood glucose control, improved quality of life and reductions in hypoglycaemic episodes, blood glucose swings, dawn phenomenon and total daily insulin dose (TDD) both in paediatric and in adult populations.14 Sensor augmented pump (SAP) therapy integrating CGM with CSII also demonstrates improved glycaemic control (average HbA1c reduction of 0.6% compared to MDI) without increased hypoglycaemia (severe hypo-glycaemia or sensor observed biochemical episodes) in children and adults, suggesting that CGM may be more successful when combined with CSII.15 During the past five years, the Juvenile Diabetes Research Foundation (JDRF) has accelerated the momentum towards closed-loop insulin delivery, marking a new era in diabetes management whereby computerised mathematical algorithms are used to link insulin delivery with real-time CGM glucose levels. Since then, studies from Cambridge have focused on overnight closed-loop insulin delivery, demonstrating approximately 20% increased time in target and reduced nocturnal hypoglycaemia, using a model predictive control (MPC) algorithm, both in children and in adults.16, 17 Others have explored the safety and efficacy of different control algorithms, intraperitoneal insulin delivery and bi-hormonal systems.18-21 Most conclude that improving insulin dosing around meals and exercise will be required to move from overnight to 24-hour closed-loop, with faster acting insulin analogues needed for optimal postprandial glucose control. Unfortunately, the evidence base for new technologies in pregnancy remains limited. Using retrospective or professional CGM, we have shown that even highly motivated T1D pregnant women (73% attended PPC, mean HbA1c 5.9% [41mmol/mol]) using MDI spent on average eight hours per day hyperglycaemic (sensor glucose >7.8mmol/L) and two hours per day hypo-glycaemic (sensor glucose <3.5mmol/L) during the second and third trimesters.22 We also demonstrated that integrating professional CGM into routine antenatal care was associated with an average HbA1c reduction of 0.6% in late gestation and reduced the risk of LGA.23 While women wore a blinded, seven-day CGM approximately four times throughout pregnancy, their sensor data were used in a standardised patient-centred fashion as an educational tool to make dietary, lifestyle and/or insulin dose adjustments. There are as yet no published randomised studies of personal (real-time) CGM in pregnancy, although a Danish study is nearing completion and an international JDRF funded study (‘Continuous glucose monitoring in women with type 1 diabetes during pregnancy trial – CONCEPTT’) will commence this year. The use of CSII in pregnancy is well established and supported by the recent NICE guidelines.7 Advocates (including these authors) believe that the benefits demonstrated in patients with T1D outside pregnancy are likely applicable before and during pregnancy. However, there is a lack of randomised controlled trials, with systematic reviews in pregnancy finding no advantages or disadvantages of CSII over MDI.14, 24, 25 Case-control studies confirm that women using CSII are more likely to attend PPC, and therefore achieve lower HbA1c levels during early pregnancy.26, 27 There are no adequately powered studies to evaluate the impact of CSII on glycaemic control during late pregnancy or on perinatal outcomes. It is unclear whether women with poor glycaemic control during the first trimester would benefit most from CGM, CSII or SAP during pregnancy. Our group has begun to refine, develop and evaluate overnight and prandial algorithms for pregnant women with T1D. The vital component of a closed-loop system for use during pregnancy is a computer algorithm which can function safely despite the physiological challenges of pregnancy – namely, changes in gastric emptying, gluconeogenesis and insulin kinetics.28 As the glycaemic control targets are tighter during pregnancy, our first steps have been to document CGM sensor accuracy and to evaluate the safety and efficacy of overnight closed-loop insulin delivery, in early (12–16 weeks) and in late (28–32 weeks) gestation. We are also using stable label isotopes to document the meal-related glucose fluxes and endogenous glucose production during T1D pregnancy. Our pilot feasibility study (CLIP-01) studied 10 T1D pregnant women (five on MDI, five on CSII) with varying levels of glycaemic control (HbA1c 5.7–8.7% [39–72mmol/mol]), diabetes duration (2–26 years) and insulin sensitivities (TDD 0.3–1.0 units/kg/day) over two 24-hour periods (12pm–12pm) during early and late pregnancy. A single CGM sensor (FreeStyle Navigator, Abbott Diabetes Care) was calibrated as per the manufacturer's instructions and inserted the day before each study visit. All women were connected to an insulin pump (Deltec Cozmo, Smiths Medical) delivering rapid acting insulin analogue aspart. At 6pm, they ate a standardised dinner (80g carbohydrate: pasta with vegetables and tomato sauce) followed by an overnight fast and a rapid acting high carbohydrate breakfast (60g carbohydrate: orange juice and toast with jam) at 7am the following morning. Prandial insulin doses were calculated by women using capillary glucose levels and their usual insulin to carbohydrate ratios. Basal insulin infusion rates were advised by the MPC algorithm and manually adjusted by a research nurse every 15 minutes. The algorithm was initiated with three CGM measurements, maternal weight and total daily insulin dose. Our results confirmed that sensor accuracy is comparable to that outside pregnancy; 94.6% of CGM glucose values were within the clinically acceptable target range (Clarke error zones A and B) with median absolute relative differences between paired sensor and plasma glucose levels of 11.4%. During the overnight period (11pm–7am), women spent on average 84% of time with plasma glucose levels within the recommended target range (3.5–7.8mmol/L) in early pregnancy and 100% of time in target during late pregnancy.29 This provides the first observational data on closed-loop insulin delivery during pregnancy, suggesting that the MPC algorithm coped well with intra-individual and gestational variability to adjust insulin delivery safely during early and late gestation. It highlighted the challenge of matching prandial insulin doses to carbohydrate rich meals, with only 47–59% of time in target after breakfast and 68–77% of time in target after dinner. We anticipate that further analyses of the carbohydrate metabolism and insulin absorption kinetics may assist prandial insulin dosing during pregnancy. Our next steps are to perform randomised controlled trials of closed-loop insulin delivery, with our subsequent study protocol (CLIP-02) incorporating two 50-minute sessions of moderate physical activity (ranging from 2.0 to 3.5 METs [metabolic equivalents]). If nocturnal near-normoglycaemia can be maintained following exercise, then progression to overnight studies in the home setting would be warranted. Technological innovations enhance many aspects of modern life (iPods, smartphones) and could mark a new era in improving the day to day life of people with T1D. While pregnant women may benefit most from recent technological advances, they have been a relatively marginalised study population. To improve health outcomes for women and their offspring with T1D, new technologies including CGM, CSII, SAP and closed-loop algorithms must be informed by scientifically rigorous data of their safety and efficacy during pregnancy, just as they are outside pregnancy. The CLIP project is funded by Diabetes UK Project Grant BDA 07/003551. HRM is funded by a National Institute for Health Research (NIHR) research fellowship (PDF/08/01/036). FreeStyle Navigator® CGM and sensors were provided free of charge by Abbott Diabetes Care. The Cambridge closed-loop studies are supported by JDRF, Medical Research Council Centre for Obesity and Related Metabolic Diseases (MRC CORD), National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and Addenbrooke's Wellcome Trust Clinical Research Centre. Thanks also to the dedicated nurses and study participants for their enthusiastic support to ensure that pregnant women are not excluded from technological advances. HRM: speaker's honoraria from Minimed Medtronic. RH: speaker's honoraria from Minimed Medtronic, Lifescan, Novo Nordisk; serves on Animas advisory panel. RH: licence fees from Becton Dickinson, and patent applications. References are available online at www.practicaldiabetesinternational.com.
AbstractThe aim of the three‐year SWEET Project EU was to establish Centres of Reference for Paediatric Diabetes in order to improve standards of care for children and young people (CYP) with diabetes across Europe. Part of this project involved making recommendations about education of CYP and their families, as well as of health care professionals (HCPs). The following UK data collected in 2009 contributed to the SWEET final data collection. Information covered diabetes education to CYP with diabetes, their families, staff in schools and HCPs. An online questionnaire was circulated to HCPs who were involved in the care of CYP with diabetes.Responses from 100 HCPs were received, mainly from larger more specialised clinics and included all members of the multidisciplinary team (MDT). Results showed that few services have written comprehensive educational curricula for CYP; programmes of education are predominantly focused on education for insulin adjustment/carbohydrate counting protocols and pump therapy, with major deficiencies in psycho‐social interventions, family communication, continuing education and transition programmes. Learning outcomes are not adequately assessed and programmes are rarely linked to diabetes outcomes.These deficiencies exist partly because paediatric diabetes has not been recognised or contracted as a specialty service. The majority of HCP posts in paediatric diabetes do not demand prior experience in the specialty. Standardised and accredited initial and continuing professional development opportunities are severely limited and often there is little support from NHS trusts. The functioning of MDTs could be improved through agreed team philosophies, consensus on targets and increased MDT ‘business meetings’. Respondents gave overwhelming support to the development of a National Paediatric Diabetes Framework that includes accredited, validated, structured education programmes for CYP, their families, schools and HCPs. Copyright © 2011 John Wiley & Sons.
AbstractAbnormal glucose metabolism is a known risk factor for coronary artery disease (CAD) and is frequently unrecognised even in patients with acute coronary syndrome. Patients with stable coronary symptoms frequently have multiple risk factors and may have no assessment of glucose regulation. The purpose of this study was to assess the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (DM) in a group of patients with stable symptoms presenting for coronary angiography. A modified oral glucose tolerance test (OGTT) was performed on 182 unselected patients undergoing elective angiography. Patients with known DM were excluded. Demographic data including cardiovascular risk factors, body mass index (BMI), and history of CAD were recorded. In all, 182 patients with a mean age of 62.1 years (±10.7 years) were studied. Indications for angiography were suspected angina. By WHO criteria an abnormal two‐hour glucose was present in 49% of individuals, with 10.4% of these patients having overt DM. An abnormal two‐hour glucose was seen in 63.2% of patients with significant CAD compared with 40.3% with normal or insignificant disease (p=0.004); 48.9% of patients with IGT or DM had normal fasting plasma glucose (FPG). In 78% of patients, BMI was over 25kg/m2. In this high risk population with multiple risk factors for CAD, previously undetected IGT and overt DM are very common. Almost two‐thirds of patients with significant CAD had abnormal glucose regulation. The use of an FPG test alone may miss a significant number of patients with unrecognised glucose intolerance. Copyright © 2011 John Wiley & Sons.
Foot disease in patients with diabetes is costly both to the individual and to the NHS. With a lifetime risk of 15% of developing a foot ulcer, foot ulcers preceding 80% of amputations and diabetes being the most common cause of non-traumatic limb amputation, it is a significant problem. Prolonged length of hospital inpatient stays and increased bed occupancy (the most common diabetes reason for admission in the recent National Diabetes Inpatient Audit)1 contribute to the financial cost of this complication. The recent publication of the National Institute for Health and Clinical Excellence (NICE) clinical guideline (CG) on the ‘Inpatient Management of Diabetic Foot Problems’ (CG 119)2 comes seven years after the previous NICE guideline which concentrated on the community and outpatient prevention and management of foot disease.3 ‘Putting Feet First’,4 guidance on commissioning specialist services for the prevention and management of foot disease in hospitals, was the catalyst for this topic to be developed by NICE under the short guidelines programme. The variation in clinical management of diabetes inpatients with foot disease was, however, of particular relevance in its acceptance as a CG topic. The short guidelines review a narrower clinical area than the full guidelines (in this case, six review questions were addressed) but are developed in a shorter period of time. Therefore prevention of foot disease is not covered with regard to the general inpatient diabetes population which is a missed opportunity. The NICE review of evidence and consequent recommendations just published will nevertheless provide a distinct advantage over other guidelines, by being NICE ‘badged’, and will provide further impetus to getting much needed recognition within the NHS for the problem of diabetes foot disease, particularly in the current financial climate. The guideline is targeted at all hospital staff who care for diabetes patients with foot disease, and is consequently relevant for staff from the emergency department on to all other inpatient areas where diabetes patients may be found. It has prioritised seven key areas for implementation covering the establishment of a multidisciplinary foot care team (MDFT) – including the need to have a care pathway, and to refer to this team within the first 24 hours of initial foot examination, the basics of foot examination, the investigation and management of foot infection and foot ulcers, and the need for patient information and support. In the current CG, best practice evidence is acknowledged as being generally either scarce or of low quality. Hence, many recommendations are based on a consensus view by the guideline development group. This lack of evidence is not unexpected, but will hopefully provide a stimulus for further studies. A few such research recommendations are suggested in the document. Similarly, only two areas are subjected to economic analysis due to the paucity of available literature. The key components of this guideline are undoubtedly the need to have an MDFT in every acute trust (whose responsibilities include managing the foot care pathway), and a recommendation on the importance of prompt referral to this team within 24 hours of diagnosing foot disease (which should normally be on admission unless a foot problem develops as an inpatient). The MDFT should have ‘the necessary skills and competencies’ needed to deliver care to the patient with foot problems, and will include key members such as a diabetologist and podiatrist among others. Surgical input is, disappointingly, not defined except to say that the surgeon should have foot expertise. However, vascular surgery is widely acknowledged in clinical practice as being vital to preventing amputations and every MDFT should push for their involvement at a very early stage in the pathway, even if not based on the same acute trust site. Similarly, podiatrists are not available in every hospital and this guideline should be used to ensure they become so. The involvement of interventional radiology and clinical microbiology is also not specified, whereas physiotherapy access and prevention of Achilles tendon contractures are listed in the key priorities section where their importance is arguably overemphasised. The recently updated National Minimum Skills Framework for the commissioning of foot care services5 should be used in conjunction with this guidance to ensure an appropriate MDFT is available for foot disease management in hospitals. Some urgency to the investigation and management of foot disease is given by the recommendation to refer to the MDFT within 24 hours, although one caveat is that the word ‘refer’ is used rather than ‘reviewed’ by the MDFT within this time frame. It will be important to see how this is implemented in practice – will the referral on a Friday evening wait until Monday morning or will the patient actually be seen ‘out of hours’? With consensus recommendations (and often lack of definitive evidence) there are inevitably areas with which some will disagree, or criticise for lacking detail or not fitting in with their own hospital practice. For instance, the recommendation to have a local hospital antibiotic protocol rather than recommending specific antibiotics is acknowledged as being due to the poor evidence available for review. However, the guideline does not help the admitting doctor (or patient) by not defining the levels of infection (other than as mild, moderate or severe), and by suggesting that oral antibiotics may be used in ‘moderate’ infections. More worrying is the advice to refer urgently in the limited circumstances of limb ischaemia, concern of deep seated infection or if systemic symptoms and signs of sepsis are present. In limb threatening infection, it is very common for the patient not to manifest systemic signs and this should be emphasised in any local pathway. The use of MRI to investigate potential osteomyelitis is, not surprisingly, recommended as being cost effective if an X-ray does not confirm its presence. However, conversely (and perhaps more contentiously) negative pressure wound therapy is only advised in the context of a trial or if the only other option is amputation. The implementation of the CG is thought to be cost neutral for the NHS. However, not all hospitals currently have the personnel to implement this guideline and, undoubtedly, many services will need to be re-organised. Nevertheless, financial savings can be made by, for example, reducing bed days, operations and expensive dressings. Therefore, this is a golden opportunity for service providers and health care professionals to highlight the need for integrated diabetes foot services in every acute hospital in England and Wales. Implementation will, of course, ultimately be of most benefit to patients when it is shown to improve clinical outcomes. There are no conflicts of interest declared.
Type 2 diabetes demands a comprehensive treatment approach in order to prevent long-term complications of the hyperglycaemic state. Central to this is the reduction of cardiovascular burden, as it accounts for 70% of deaths in people with type 2 diabetes.1 The ACCORD and ADVANCE studies were large, randomised, controlled trials designed to establish the benefits of near normal glycaemic control on cardiovascular events and risk of death in people with established type 2 diabetes.2, 3 Since the premature termination of the glycaemic control arm of the ACCORD study 18 months early, there has been great interest in the role of intensive glycaemic control in type 2 diabetes.4 In the primary publication of the ACCORD results, the investigators were unable to explain the increase in total mortality in the intensive treatment group. They indicated that this was not due to rosiglitazone or hypoglycaemia, but did not supply any data to support these suggestions. Several recently published post-hoc analyses from the ACCORD5-9 and ADVANCE10 trial groups seek to address some of the issues. Two post-hoc analyses of data from the ACCORD study were published back-to-back in the British Medical Journal.5, 6 The first aimed to investigate possible determinants of severe hypoglycaemia during the study, including baseline characteristics, and also the association of severe hypoglycaemia with achieved HbA1c concentrations during therapy.5 In the ACCORD trial, participants were asked to report episodes of hypoglycaemia within 24 hours; the tracked episodes of severe hypoglycaemia were defined as an episode, requiring assistance of another person, with associated plasma glucose of less than 2.8mmol/L, or quick resolution with either oral or intravenous glucose or glucagon. The annual incidence of severe hypoglycaemia in the intensive treatment group was 3.14% compared to 1.03% in the standard treatment group. Baseline subgroups identified as being at a significantly increased risk of severe hypoglycaemia included women, African-Americans, those with less than a high school education, older participants, and those using insulin at trial entry. The risk of severe hypoglycaemia was not associated with the rapid reduction in HbA1c in the first four months of the trial but was, interestingly, associated with an increase in HbA1c concentration in both treatment groups. The risk of severe hypoglycaemia increased with each 1% rise in HbA1c concentration. The second BMJ publication aimed to determine whether there was a link between hypoglycaemia and mortality in the study.6 Severe hypoglycaemia was indeed associated with increased risk of death; however, surprisingly the risk of death was lower for participants in the intensive arm than in the standard arm. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study3 also sought to determine the benefits of intensive glycaemic control (target HbA1c of 6.5% [48mmol/mol]) on macrovascular events. The approach to improving glycaemic control in ADVANCE was more relaxed than in ACCORD and allowed HbA1c to fall gradually (0.5% vs 1.5% HbA1c drop in six months). Again, the rates of severe hypoglycaemia were higher in the intensive treatment group (2.7% in the whole study) compared to the standard treatment regimen (1.5%). Contrary to the ACCORD study, it did not find an increased mortality with intensive glycaemic control. The primary endpoint, which was a composite of microvascular and macrovascular endpoints, was significantly reduced, and most of the reduction was in microvascular outcomes.11 Further post-hoc analysis found a strong relationship between severe hypoglycaemia and vascular events or death.10 In patients reporting severe hypoglycaemia, the mortality was greater in the standard treatment group (5.1%) than in those assigned to intensive treatment (3.6%). For participants without severe hypoglycaemia annual death rates were similar: 1.9% in the standard group and 1.8% in the intensive group. Severe hypo-glycaemia was also associated with macrovascular events, microvascular events and a variety of other adverse outcomes including disorders of the respiratory and digestive systems. The study identified the following factors assoc-iated with increased risk of hypoglycaemia: older age, longer duration of diabetes, higher creatinine levels, cognitive dysfunction, lower body mass index, use of multiple oral hypoglycaemic agents and assignment to intensive control. The authors were not able to identify a causal relationship between severe hypoglycaemia and mortality, although impaired cardiac autonomic function was cited as a possible factor. More likely it was thought that severe hypoglycaemia is a marker of vulnerability and should signify those at risk of an adverse event including death. Those with significant hypoglycaemia should therefore be targeted for optimisation of their diabetes care and support. Having failed to find a clear explanation that the increase in mortality was due to hypoglycaemia, three further publications in Diabetes Care explored patient characteristics at baseline and during the study.7-9 In the first, baseline self-reported neuropathy, aspirin use, and a higher baseline HbA1c identified a differential effect on mortality.7 In a separate, later publication, baseline diabetic autonomic neuropathy, detected using a battery of tests, was associated with an increased mortality.8 The third, and strangest, of the Diabetes Care publications looked at effects of HbA1c during the study.9 Higher average HbA1c was associated with increased risk of death. Analysis of the population in the intensive glycaemic control arm (HbA1c target <6% [42mmol/mol]) revealed that mortality risk was linearly associated with HbA1c, whereas mortality risk increased in the standard control group (HbA1c target = 7–7.9% [53–63mmol/mol]) when the HbA1c was greater than 7%. Mortality was increased in patients in the intensive treatment group whose HbA1c remained high for the duration of the study. In particular, risk of death was increased when little or no decrease in HbA1c was seen in the intensive group in the first 12 months of the study. In the discussion, several potential reasons for an association between higher HbA1c and mortality in the intensive control group are suggested. The authors suggest that characteristics of the participants that were not measured might be involved, including ‘behavioural issues’ such as lack of adherence to medical advice, depression or other psychiatric conditions, abnormal cognitive function, and social or financial crises. This highly speculative suggestion, which has no support from any of the data so far published from the ACCORD trial, seems to suggest that the problems were with the patients and not the study design. Finally, a recent point-counterpoint review in Diabetes Care has offered the suggestion that the increased mortality in the intensive treatment group represents no more than a chance finding,12 a suggestion that has been refuted by one the principal investigators of the ACCORD trial.13 The approach to the management of type 2 diabetes should remain multifactorial and include glycaemic control with HbA1c target of 7% (53mmol/mol) given that higher HbA1c concentrations are associated with increased mortality. When comparing the strategies used in these two large trials it seems the more conservative HbA1c lowering approach of ADVANCE may be more suitable in type 2 diabetes, particularly if present for several years. The dramatic HbA1c reduction of ACCORD employed extensive use of the thiazolidinedione rosiglitazone (used in around 90% of those in the intensive control group) and insulin, whereas ADVANCE ensured gliclazide use at baseline. In addition to mortality, the trials had differing weight gain with far more weight gain (3.5kg) seen in the ACCORD intensive control group at completion. This weight gain may be related to choice of hypoglycaemic agents. A recent meta-analysis14 included these trials along with UKPDS, VADT and PROactive to evaluate the benefit of intensive glycaemic control on cardiovascular events and all-cause mortality with data from 33 040 patients. Participants in the intensive control groups had a mean HbA1c 0.9% lower than standard therapy at follow-up (6.6% vs 7.5% [49mmol/mol vs 58mmol/mol]). Intensive glycaemic control was found to confer a 17% reduction in non-fatal myocardial infarction but had no effect on all-cause mortality. Given the wealth of evidence supporting blood pressure control, statin use and aspirin when indicated, and the comparative ‘safety’ of these relative to recurrent severe hypoglycaemia, glycaemic control is an important adjunct to cardiovascular risk modification, but so far is not the holy grail in patients with established diabetes. Glasgow Royal Infirmary was a centre for the ADVANCE study. Prof Fisher was the principal investigator for the centre and a member of the ADVANCE collaborative group.
AbstractBariatric surgery is an important treatment for obesity and most patients enjoy substantial improvements in coexisting type 2 diabetes (T2D). As a result of the historic failure to establish relevant long‐term controlled trials, however, there is a need to separate evidence from unfounded belief. The short‐term impact, operative morbidity and mortality rates, and potential long‐term surgical and metabolic side effects of most (but not all) of the common forms of bariatric surgery are reasonably well described. In contrast, the longer‐term evidence base for applying bariatric surgery as an approach to treating T2D is much weaker. While bariatric surgery may have a prolonged beneficial effect on hyperglycaemia, it also has risks, and its economics and sustainability are unproven. At the more fanciful end of opinion is a mismatch between expectation and reality, with the risk that patients' expectations may be unrealistically raised. Long‐term relapse of weight and hyperglycaemia are well‐recognised and patients who choose these treatments will never be free of medical supervision.The only way to guarantee that appropriate patients with T2D are safely selected for bariatric surgery, offered an appropriate choice of evidence‐based procedures, and receive appropriate immediate and long‐term postoperative medical care is for diabetologists to take on this mantle of responsibility. Copyright © 2011 John Wiley & Sons.
‘All change in history, all advance, comes from nonconformity. If there had been no troublemakers, no dissenters, we should still be living in caves.’ (AJP Taylor.) In the November/December 2010 issue of Practical Diabetes International, MEJ Lean's personal comment reported on ‘How not to die from diabetes in a mountain hut’. His experiences involved an extreme encounter with a 40-something male insulin-dependent Englishman who went into a near fatal hypoglycaemic coma among fellow mountain skiers and climbers in an isolated glacial region of France. After many sugar lumps and jam sandwiches the Englishman ‘survived’ what could have been a ‘totally predictable, [yet] preventable, near fatal crisis’. The Englishman also put his other comrades at risk. To add insult to injury, the survivor did not even ‘know the name’ of his consultant at a well known London Hospital, part of the conclusion being his diabetes care was woefully inadequate. Professor Lean states that we should learn some lessons from this experience, the ‘keystone’ being better education and experienced professional guidance. I wonder if a (diabetes) psychotherapy perspective could add anything to this encounter? As Anderson1 states, information transfer as a way of encouraging good self-care reflects a narrow view of human behaviour. Human behaviour and health behaviour are made up of many components, including psychological processes. These are beginning to be understood in terms of the role they play when patients reject or resist aspects of diabetes management and care. Unfortunately (or fortunately, see above), many type 1 diabetes patients I have seen for psychotherapy because of their ‘chronic poor control and complications’ are very much like our friend. Overall, it seems that this patient who engaged in an ‘extreme sport’ was extremely ill-prepared or even neglectful in terms of his condition. He seemed to act as if he did not have diabetes. There was minimal kit but no glucagon and no record of blood glucose results, and he carried no guidance notes on diabetes or hypoglycaemia. In fact he had ‘never heard of glucagon’ (that's why he didn't carry it?); he put himself and others at risk. This article made me think about those who engage in high risk activities, some of whom are thought of as type A personalities. Action orientated, the persistent, time urgent, impatient risk takers of the psychological spectrum draw energy from action – while reflecting on consequences after the event: ‘embarrassment’ in this particular case. Freud wrote of the innate death drive in this regard, but today risk takers can be seen as either courageous or crazy. Skydiving, cliff jumping and lone sailing are also activities of the type A person, although in the diabetes psychotherapy clinic we see more mundane associations with poor glycaemic control and multiple episodes of hypoglycaemia: unprotected sex, gambling and drug taking. Although type As enjoy the camaraderie uniting them with others involved in high risk activities, they are essentially individual-istic and often secretive, as reflected in this case; in particular, their only fear is of the mundane – and of needing advice and support. In this regard, our patients often perceive their diabetes as a mundane activity which they treat with contempt and therefore reject (resist and deny). Full acknowledgement of their condition would result in full engagement with their physicians and diabetes specialist nurses which, by definition, they also resist. They may turn up for annual review but it is unlikely they would ask: ‘How do I keep myself safe on a mountain top?’ Let's just say, this patient turned up to his ‘well known’ London diabetes annual review and did not receive his doctor's name (likely?!). Why did he not ask for it or remember it if given? I would like to suggest that he was not motivated to do so. He was ‘resistant’. Resistance and denial co-exist. They are employed by the mind to reduce the risk of stress via the avoidance of ‘problem confrontation’. However, they are regarded as ineffective ways of dealing with problems and in health psychology lead to high risk health behaviours. This patient is clearly lucky to be alive. This Englishman is involved in high risk activities via sport and health care. Passively resistant and actively defiant cases have been outlined elsewhere.2,3 It is a form of pseudo freedom which many of our patients engage in. Strategies derived from learning theory will not help or change behaviour such as this as they do not consider unconscious drives in the process of decision making. A disease-focused psychotherapeutic approach may do more to keep risk takers safe (enough) than education and guidance. Then we can have all of the action and all of the content.
A new report, ‘Commissioning Specialist Diabetes Services for Adults with Diabetes’,1 has been released, based on the work of a Diabetes UK multidisciplinary Task and Finish Group which aimed to define, for the first time, the roles, responsibilities and components of specialist diabetes services so that they might continue to effectively provide for the needs of people with diabetes. The group met from 2008–10 and contained representatives from the Council of Health Professionals of Diabetes UK, the Association of British Clinical Diabetologists, Community Diabetes Consultants, the Primary Care Diabetes Society, DISN UK Group, TREND UK and the Diabetes Nurses Forum. The content of the document has been endorsed by all these organisations. The need for such guidance lies in the considerable change in the organisational requirements of specialist diabetes care over the past 10 years in the NHS. This has been driven by a combination of several factors, including the increasing prevalence of diabetes due to rising levels of obesity and an aging population, which have placed an enormous demand on health care services. This has been coupled with publication of national standards for diabetes in the form of the National Service Framework (NSF)2 and the introduction of incentive payments to primary care for achievement against selected indicators of diabetes care (that is, the Quality and Outcomes Framework, QOF). There have also been significant changes in health policy, specifically the drive to move non-specialist diabetes services into the community, the change to tariff-based payments for hospital care and the evolution of practice-based commissioning. This has led to several welcome improvements in the management of diabetes in primary care settings, as manifest by reports based on QOF returns for the nation with many services, previously provided only by specialists, now provided by non-specialists in community settings, such as insulin initiation and titration.3 However, such developments have also led to the question as to what role specialist diabetes services ought to play in the management of diabetes care within a community, and the document addresses exactly this issue. This piece of work is particularly timely in light of the publication of the new ‘Equity and excellence: Liberating the NHS’ health White Paper4 which will place most of the NHS budget in the hands of general practice (GP) consortia that will be responsible for commissioning health services for the local population. This has significant implications for diabetes care as concerns exist as to whether GP commissioners, who will be generalists rather than specialists, may initially lack familiarity with the diabetes specialist care services required to meet the needs of a local population. The document should assist commissioners, health care managers and specialist health care providers by providing advice on the structure of specialist diabetes services for adults to ensure that people with diabetes receive the right care in the right place at the right time. The report defines specialist diabetes services in the context of a whole diabetes health care system, and emphasises that a collaborative approach should be taken by agreement of an integrated model of diabetes care by all stakeholders, in line with recognised best practice.5 It also highlights the role of managed diabetes networks in developing, implementing, managing and monitoring this. There is a recognition that specialist teams may need to provide services in a range of health care settings consistent with the ethos espoused in the ‘Teams without Walls’ philosophy.6,7 The role of specialist diabetes services within this agreed model of care will usually consist of delivery of direct clinical outpatient and inpatient care, leadership and coordination, provision of education and training, and research and innovation. While it is accepted wisdom that only people with diabetes who have ‘complex’ care needs ought to be managed in a specialist outpatient setting, in practice it has previously been unclear as to how this group of patients could be defined. These ‘complex’ needs are described using existing NSF standards or certain logical principles; for example, if a service requires liaison between the diabetes team and another specialty (such as obstetrics, vascular or nephrology) then it could be defined as ‘complex’ and should be managed by specialist care. Another core role for specialist teams is provision of inpatient care, and acute trusts should support the development of diabetes specialist inpatient care teams to reduce expected length of stay and ensure delivery of safe person-centred care. Diabetes specialists (particularly consultant diabetologists) are best placed to provide leadership and advise on strategic planning for diabetes services across a locality. This role should be commissioned and supported with dedicated sessions. In addition, specialist teams are likely to continue to initiate and conduct the majority of diabetes related research and innovation, and also will have a responsibility to help teach, develop and maintain the skills of other care teams, including provision of support to primary care. The dictionary definition of a specialist is ‘a person highly skilled in a specific field’ and the report describes the qualifications, experience and competencies that the various members of a diabetes specialist team should have in order to be able to describe themselves as a ‘specialist’. Such team members include consultant diabetologists, diabetes specialist nurses, diabetes specialist dietitians, diabetes specialist podiatrists, diabetes specialist pharmacists and GPs with a special interest in diabetes. The full document also defines components and service specifications for many core specialist diabetes services including diabetes pregnancy, diabetes transitional care, diabetes foot, diabetes ophthalmology and diabetes renal services. While patients with complex care needs may comprise a minority of the diabetes population, they invariably have poorer health outcomes and consume disproportionate amounts of health care resources, especially time. It is therefore incumbent on commissioners of diabetes services to ensure that the health needs of this population are met, and for specialist providers of diabetes care to ensure that their services meet the required standards. We hope that readers will endorse the contents of this report which hopefully will be used in conjunction with the existing ‘Diabetes Commissioning Toolkit’6,8 in order to meet this challenge. There are no conflicts of interest.
Benchmarking can be a useful method to improve standards of health care. Comparisons of outcomes between different hospitals and regions, if performed and interpreted correctly, can be used to explore ways of identifying deficiencies in care and to help improve processes to benefit health care delivery. A new NHS Atlas of Variation for England has been published, and it states: ‘Our aim is to put variations in activity, expenditure, quality, outcome, value, and equity firmly on the health service agenda for the next decade and to stimulate the NHS to search for unwarranted variation and, by extension, to tackle the causes and drivers of that variation.’ In terms of endocrine problems, the Atlas reported on diabetes-related amputations, the percentage of people recorded as receiving nine key diabetes care processes, and rates of bariatic surgery.1 For amputation the results show a variation from around 1.5 per 1000 patients with type 2 diabetes undergoing lower extremity amputation in South East England and the West Midlands to 3 per 1000 patients in South West England. The percentage of patients receiving nine key care processes in diabetes varied from 2% to 70% across all primary care trusts in England. What factors may contribute to a two-fold variation in amputation and a 35-fold variation in process of care? Firstly, it should be asked whether the association is due to artefact or is a real association that does not appear to be explained by chance, bias or confounding. It is also crucial to consider whether the measurement is an appropriate reflection of quality of care. Using amputations as an example (Atlas map 3) it is important to recognise that although amputations are a reasonable guide of foot care, early amputation can sometimes be a better outcome than delayed or absence of amputation2 which may even precipitate early death. Secondly, the interpretation of the data needs examining. The data presented are adjusted for differences in the distribution of age and sex between different populations. However, other variables, such as deprivation, smoking status and ethnicity, which are known to be associated with risk of amputation and vary by region and could therefore confound the association, do not appear to have been considered in the comparisons of amputation rates. It may be that regions with lower amputation rates have diagnosed more patients with early onset in diabetes. In itself this is not a bad thing, but it will increase the denominator when calculating the rates of amputation. This results in a lowering of rates due to a statistical quirk rather than anything to do with improved foot care. It would thus be useful to know the adjusted prevalence of diagnosed diabetes in each region, or the rates of amputation per total population, as this would help in the interpretation of the data. Additionally, many patients in hospital with diabetes and co-existing conditions are not recorded as having diabetes.3 Rayman showed that only 74% of patients with diabetes undergoing amputation were recorded as having diabetes,4 and recent data from Scotland indicate that the proportion of people with diabetes who had diabetes recorded in routine hospital data varied from 34–88% between hospitals5 reflecting a large variation in a relatively small geographical area. In addition, many patients, who were diagnosed as having diabetes during the admission that led to an amputation, may not be recorded on discharge data as having diabetes. The use of routine collected clinical data to make comparisons between regions may also contribute to some of the variation observed in analyses as data are collected in different ways. Thus, the data need to be interpreted with some caution. However, although part of the variation may be due to inaccuracy, it is likely that part is real and there is consensus that improving diabetes care and reducing amputation rates are desirable outcomes. The logical follow-on question is ‘how can best practice be shared?’ Initially, the focus should be on evidence-based practice, as evidence-based health care is most likely to be robust in the delivery of benefit over the long term.6,7 Multidisciplinary foot clinics (MDFCs) have been shown to reduce amputations.8,9 The NHS Atlas reports the changes in amputation rates after introducing MDFCs in Ipswich and Torbay, with at least a three-fold reduction,10 and locally we report a reduction in amputations at a time when an MDFC was introduced.11 MDFCs are complicated to organise. Although an increase in resource is often required, more efficient use of current resource and cross-disciplinary cooperation can contribute a great deal towards an effective service. One likely benefit of an MDFC is that it acts as a focal point for many of the other evidence-based benefits in foot care such as total contact casting, negative pressure wound therapy and others.7,12 Screening has been shown to effectively identify the patient at risk,7,13 thus allowing scarce resources to be targeted towards those at greatest need. The long-term benefits of addressing risk factors, such as glycaemic control, hypertension, dyslipidaemia and smoking, should not be underestimated. Patients at greatest risk of amputation appear to be those with ischaemic feet and infection.14 Observational studies have demonstrated the benefit of early vascular intervention.15-17 Regions with higher rates of amputation should be encouraged to explore the accessibility of rapid vascular intervention services, and to see if they link with diabetes services effectively. Unfortunately, there are few data on randomised control trials (RCTs) of vascular interventions in patients with diabetic foot ulcers,7 and such an RCT is urgently required. For infected foot ulcers, empirical antibiotics should be started early using the knowledge of local microbiological sensitivities, and changing the antibiotic when the results of specific sensitivities become available. General practitioners and hospital practitioners need to be aware of the need for early use of high dose antibiotics, and in this regard local antibiotic policies18 can be useful. For processes of care (Atlas map 4), when the top and bottom 5% of primary care trusts (health care based population groupings of which there were approximately 150 in England at the time of the analysis with populations varying between 90 000 and 1.3 million people) are removed from the analysis, the variability drops from 35-fold to five-fold. The appropriateness of these ‘measurements’ being assessed may be more debateable than with amputation, but as some of these data are linked to payments for general practitioners they may be more accurate. It is notable that clinicians have a very varied response to incentivised target-based schemes. Furthermore, although there may be an improvement in these measurements in all areas, with a mean improvement for the population as a whole, the differences between the best and the worst areas, and hence the variation, may increase. Thus, increased variation should not be mistaken for deteriorating levels of care. We live in an era where guidelines proliferate, but the evidence is often limited and the implementation of the recommendations frequently fails. The NHS Atlas of Variation1 is a pointer towards this, and such benchmarking should be used as a tool to spread best practice across all areas. The information should be used in a constructive dialogue and a genuine desire to resolve unnecessary barriers to care. The temptation to use such data as a competitive league table needs to be strongly resisted, and areas with poorer outcomes need to be supported to identify the explanations for their outcomes and to help improve their own services. There are no conflicts of interest.
Approximately half a million people die in the United Kingdom each year, of whom more than three-quarters are aged 75 years and over. Calculations based on the prevalence of diabetes indicate that 6–9% of those dying will have diabetes. In ethnic minority groups the prevalence will be significantly higher and in all groups the majority will have type 2 diabetes. Accurate data on the incidence of diabetes as a contributory factor to death are not available due to the vagaries of death certification. Excellent end of life care (EOLC) strategies such as the Liverpool Care Pathway for the Dying Patient are already in routine use. The aim of this position statement is to augment such EOLC tools with guidance specifically related to people with diabetes, their families and carers. Outside the scope of this statement are issues relating to the use of advance directives (although patient autonomy and choice are paramount at all times), preferred models of palliative care services to support patients with diabetes, and referral criteria for hospice care. Historically, the diabetes community has pioneered a patient-centred approach to care but the care of the dying patient with diabetes has been neglected and needs to be incorporated into our practice. Sensitive and timely sharing of information around the potential impact that diabetes can have both on quality and quantity of life is important, and open discussion with user groups will be of major importance so that dying patients can be truly empowered in their decision making. The multidisciplinary diabetes team (MDT) will need to be proactive in recognising the onset of a patient's terminal decline in health, and liaising with the appropriate EOLC services. Conversely, those providing EOLC should ensure that the diabetes team is aware of the patient so that specialist guidance on the management of diabetes can be provided. EOLC services are focused on high quality end of life care, symptom management and the provision of psychosocial support with an agreed set of criteria to identify those who require urgent palliative care support worker responses in different situations, e.g. unresolved pain, rapid discharge from hospital or care breakdown at home. When palliative care is instituted there are several elements of particular relevance to those with diabetes. Unnecessary tests such as frequent blood glucose monitoring and complex insulin regimens are burdensome and should be avoided. An intervention required during relative health may not be indicated for the dying, with the caveat that patient preference is always of overriding importance. Patients, families and carers will often have spent many years striving for tight glycaemic control in an attempt to reduce the risk of long-term complications. They may find it difficult to understand that, when the end of life is imminent, maintenance of strict euglycaemia can be detrimental to quality of life and the avoidance of long-term complications becomes an irrelevant goal. Both patients and careers may require sensitive counselling from members of the MDT to explain the shift in glycaemic goals. Nevertheless, it is important to maintain adequate control to enhance comfort by preventing hyperglycaemia-induced thirst, dehydration, confusion, drowsiness and symptomatic hypoglycaemia. Many elements presenting at the end of life predispose to alteration of glycaemic control; hyperglycaemia may result from, for example: • The stress response to severe illness. • Disturbance in glucose metabolism caused by certain malignant tumours. • Use of steroids for symptom relief. • Co-existent infection. The insulin requirement may be reduced, with the consequent risk of hypoglycaemia as a result of, for example: • Weight loss. • Anorexia leading to malnourishment. • Renal and/or hepatic failure. Oral hypoglycaemic agents may no longer be required and the involvement of an experienced dietitian can be invaluable for those with poor food intake. In many instances, diabetes is a co-morbidity in patients with a terminal illness such as cancer. Treatment regimens should be tailored to each individual by those with appropriate skills, in consultation with the patient and their carers. Certain diabetes-related symptoms/complications may be exacerbated in those with terminal illness, for example: • Pain (combination of neuropathic and bone pain). • Constipation (combination of autonomic neuropathy and opiate-induced effects). • Fatigue (effects of hyperglycaemia and malignancy). The aim should be to avoid symptomatic hyper- and hypoglycaemia with a minimum of blood glucose monitoring. A target range for blood glucose of 5–15mmol/L is appropriate and detailed treatment algorithms are best avoided. Early involvement of the specialist diabetes team for individualised advice is advocated. This is a disease of absolute insulin deficiency; therefore insulin withdrawal is likely to lead to death. Unless a patient is entering the final phase of life (embarking on the EOLC pathway) we would recommend the continuation of insulin with the regimen simplified wherever possible unless the patient specifies otherwise. Suggested options are: • Twice-daily fixed mixture. • Twice-daily isophane insulin. • Once-daily long-acting analogue. If a mentally competent patient requests withdrawal of their insulin, this should be respected. Blood glucose monitoring should be kept to a minimum (once or twice daily). Insulin-treated patients with type 2 diabetes without symptomatic hyperglycaemia may be able to discontinue insulin. Should the individual become symptomatic, a simple insulin regimen can be reintroduced such as once-daily long-acting insulin analogue or twice-daily isophane. Tablet-treated patients may also be able to discontinue treatment as a reduction in food and fluid intake leads to lower blood glucose levels and may increase the risk of hypoglycaemia. Blood glucose monitoring should not be performed in these patients unless there are plans to adjust treatment based on the blood glucose results or it is the patient's preference. High dose steroids may be prescribed for symptom relief. Depending on the frequency of dosage, patients may experience a rise in blood glucose 2–3 hours after steroids are given, returning to baseline levels about 12 hours later. A single injection of isophane insulin given with the steroids is often sufficient to avoid symptomatic hyperglycaemia. Involvement of the specialist diabetes team is recommended if more complicated insulin regimens are required. Although life expectancy for people with diabetes is increasing, many will die prematurely as a result of diabetes-related end organ failure. The subject of proximity of death is rarely broached with individuals suffering severe complications of diabetes, thus denying them the chance to express their wishes for end of life care. Identifying individuals who are entering their last 6–12 months of life is difficult both medically and emotionally, and health care workers need to examine the reasons why they may shy away from these emotional encounters. There are some well recognised generic indicators of poor prognosis of which those working closely with patients with diabetes should be aware so that appropriate discussion and care planning can be initiated. These include the presence of: • Multiple co-morbidities. • Non-intentional weight loss of >10% over six months. • General physical decline. • Serum albumin <25g/L. • Dependence in most activities of daily living. This position statement does not cover the specific modalities of death that occur with an increased frequency in those with diabetes because, by definition, they cannot be anticipated and therefore an EOLC strategy is not appropriate. However, knowledge of their existence may help those dealing with the bereaved in the aftermath of the death of a patient with diabetes. Both ‘Dead in Bed’ syndrome and sudden in-utero fetal death, although rare, are more common in people with diabetes; the exact aetiology in both cases has yet to be established. As the population of the UK ages and the incidence of diabetes rises, more individuals will be reaching the end of their life with co-existent diabetes. In the words of Prof J Saunders, diabetologist and ethicist: ‘Dying patients should receive care that offers comfort, dignity and freedom from distressing symptoms as far as these are possible.’ That includes those with diabetes for whom the aim should be to keep the blood glucose within a range which will avoid symptoms while reducing invasive tests, such as blood glucose monitoring, to a minimum. This position statement offers some guidance for the management of diabetes during the end stages of life and hopes to trigger discussion within the multidisciplinary diabetes teams relating to their role in EOLC. The MDT should engage with user groups and primary and secondary care colleagues to enhance the provision of end of life care for patients with diabetes for whom we are both carers and advocates. There are no conflicts of interest. Readers can go to the following websites and retrieve information on end of life care in diabetes: • www.diabetes.org.uk. • www.diabetes.nhs.uk/commissioning. • End of Life Care Strategy – promoting high quality care for all adults at the end of life. Department of Health, July 2008. • Marks JB. Addressing end-of-life issues. Clin Diabetes 2005; 23(3): 98–9. • Vandenhaute V. Palliative care and type II diabetes: A need for new guidelines? Am J Hosp Palliat Care 2010; 27(7): 444–5. Epub 2010 Apr 13.
The prevalence of diabetes mellitus is significantly increasing. Since 1996 the number of people diagnosed with this condition in the UK has doubled from 1.4 million to 2.8 million. By 2025 it is estimated that over four million people will be diagnosed with diabetes.1 This increase is attributed to the ageing population and the obesity epidemic. Glucose tolerance progressively declines with age. Less than 1% of male adults under 25 years old have diabetes, but almost 30% of over 65-year-olds suffer from this disease.1 Type 2 diabetes comprises 90% of people diagnosed with diabetes mellitus. It is characterised by the body's inability to secrete insulin from the pancreatic β cells and/or the body's inability to respond to the physiological action of insulin. Type 2 diabetes is a multi-factorial disease, with interacting genetic and environmental factors. β cell function2 and proliferation3 are both negatively regulated by age as is insulin sensitivity.4 Therefore function of the two main components underlying glucose homeostasis (insulin production and action) declines with age. Additionally, several diabetic risk factors are associated with ageing, including increased adiposity and decreased physical exercise.5 These factors are likely to contribute to the development of age-related insulin resistance, reduced glucose tolerance and type 2 diabetes. Current environmental factors such as diet, physical activity and smoking contribute to an individual's risk of developing type 2 diabetes. However, there is accumulating evidence that nutrition during fetal and early postnatal life can cause permanent adaptions to the structure and function of specific organs. These changes appear to influence the risk of developing type 2 diabetes and other metabolic diseases. Over 40 epidemiological studies carried out worldwide have confirmed the association between birth weight and development of disease in adult life. Birth weight is a crude reflection of fetal growth and low birth weight is associated with alterations in the structure and function of essential organs. The first evidence linking fetal development with type 2 diabetes arose from a study by Hales and colleagues in 1991. They studied a cohort of Hertfordshire men born between 1911 and 1930 and observed an inverse relationship between birth weight and impaired glucose tolerance (a pre-diabetic state) and type 2 diabetes. The individuals with the lowest birth weight had a six-fold increased risk of developing type 2 diabetes compared to the heaviest.6 These low birth weight individuals also had an 18-fold increased prevalence of the metabolic syndrome. Hales and Barker proposed that, in conditions of poor fetal nutrition, the fetus would protect the development of particularly vital organs, such as the brain, at the expense of other tissues, such as the endocrine pancreas. This proposal was termed the 'Thrifty Phenotype Hypothesis'. In agreement with this hypothesis, human pregnancies complicated by severe intrauterine growth restriction show a reduction in fetal endocrine pancreatic tissue and insulin producing β cells compared to controls, with brain growth being spared.7 In 1997, a study of Danish dizygotic (non-identical) and monozygotic (identical) twins in their 60s showed that the diabetic twin was the twin which had the lower birth weight. The study authors concluded that low birth weight and the risk of developing type 2 diabetes was at least partially independent of genotype as this association was seen in monozygotic as well as dizygotic twins. This supported the importance of intrauterine conditions.8 These results have been replicated in other large scale population studies in Italy and Sweden.9,10 The Dutch Hunger Winter provides a unique opportunity to study a direct link between reduced maternal nutrition during specific periods of gestation, with long-term consequences for the offspring's health. In the winter of 1944–5, food supply into the western part of the Netherlands was restricted to 400–800 calories. Individuals in utero during the famine had a low birth weight and a decreased glucose tolerance at the age of 50 compared to individuals born the year before or after the famine.11 Notably, glucose tolerance was decreased the most among individuals exposed to famine in mid or late gestation. If the individual had become obese as an adult, the effect on glucose tolerance was exacerbated.11 There are a large number of well-established animal models that have indicated a link between fetal growth, early postnatal growth and long-term metabolic diseases. These have been used to try and clarify the physiological and molecular mechanisms linking events during this critical period of development and long-term health. Dietary manipulations include reduction in overall maternal caloric intake, maternal high fat feeding, maternal anaemia, maternal obesity and maternal protein restriction. Other insults include intrauterine artery ligation as a model of placental insufficiency, maternal diabetes resulting from streptozotocin administration, which ablates β cells in the pancreas, and fetal exposure to glucocorticoids and hypoxia have also been studied (reviewed in McMillen et al.).12 Despite the differences in model design, the resulting phenotypic outcomes in these models are remarkably similar. This suggests that a range of disruptions in the fetal and early postnatal environment may act through a common pathway to produce a similar adult phenotype, especially in relation to glucose tolerance. The genetic code of the cell regulates which genes have the potential to be produced, but epigenetic modifications affect the level of expression of these genes. These epigenetic marks are achieved through methylation of cytosines in CpG islands (often in the promoter of the associated gene) and specific molecules binding to histone tails, which remodel chromatin structure. These modifications of histones include methylation, acetylation, phosphorylation and sumoylation. The combination of these epigenetic marks is responsible for determining whether a region of DNA and, therefore, specific genes are active or repressed. While the genotype is identical in each cell of an organism, the active and repressed epigenetic marks of the genes collectively lead to an epigenetic code or epigenotype, which is tissue and cell specific. This gives the organism a degree of phenotypic plasticity with a fixed genotype and, therefore, genes can be locked in active or repressed states depending on the needs of the cell, making it a prime target in the field of developmental programming.13,14 Monogenic autosomal dominant mutations in maturity-onset diabetes of the young (MODY) genes have been implicated in the development of diabetes. These genes cause impaired insulin production and/or secretion in the pancreatic β cells. One of these genes, hepatocyte nuclear factor 4-α (HNF-4α) is a transcription factor from the nuclear hormone superfamily. It is crucial for pancreatic β cell differentiation and glucose homeostasis,15 and is linked to the development of type 2 diabetes.16 This makes HNF-4α a promising candidate gene for epigenetic regulation. Using a well-established rodent model of maternal protein restriction during the prenatal and lactational periods, the role of epigenetic regulation of HNF-4α in mediating developmental programming effects was recently investigated. In this model, rat dams are fed an isocaloric low protein diet (80g/kg) compared to a control diet (200g/kg). The low protein offspring have a modest reduction in birth weight, around 15% reduced compared to controls.17 They demonstrate organ selective growth, as proposed in the thrifty phenotype hypothesis, with the pancreas, muscle and liver showing the greatest reduction in weight compared to controls while brain weight is maintained.18 In the pancreas, there is a reduced number and size of islets compared to controls, along with dramatically reduced islet vascularisation at birth19 and insulin secretion.20 They then undergo an age dependent loss of glucose tolerance more rapidly than controls, developing insulin resistance by 15 months21 and have frank diabetes at 17 months of age.22 Sandovici and colleagues demonstrated that HNF-4α is epigenetically regulated by maternal diet and ageing in rat islets. Exposure to inadequate nutrition during critical periods of growth led to epigenetic silencing at an enhancer region of the gene. This weakened the promoter-enhancer interaction resulting in a reduction in HNF-4α expression. Simultaneously, the entire HNF-4α locus in the islets is progressively silenced epigenetically during ageing, an effect that is more pronounced in rats exposed to suboptimal maternal nutrition. This study therefore demonstrated that nutrition during early development influences the dynamics of age-associated epigenetic changes, at the HNF-4α locus to influence an individual's susceptibility to type 2 diabetes later in life.23 This may represent a more general molecular mechanism by which nutrition during critical periods of development can influence risk of age-associated diseases. There are no conflicts of interest declared.
A 52-year-old man was referred with a 15kg weight loss over eight weeks associated with loss of appetite, nausea and early satiety. The day before admission he developed numbness and pins and needles in his left foot. He had hypertension and diabetes which was diagnosed three years previously. His control was very good with latest HbA(1c) of 6.6% (49mmol/mol) on metformin only. He had no evidence of microvascular complications. He had extensive investigations which included CT head, thorax, abdomen and pelvis, tumour markers, prostatic specific antigen, autoantibody screen and protein electrophoresis, which were all normal. Nerve conduction studies and electromyography confirmed right ulnar neuropathy and showed non-specific neuropathy in the lower limbs. A diagnosis of diabetic neuropathic cachexia was made.It is important for this condition to be recognised and considered in patients with diabetes mellitus in order to avoid unnecessary and lengthy investigations. Copyright (C) 2011 John Wiley & Sons.
Given the nature of diabetes as a long-term condition, much of what we do in our profession has been determined by evidence from large, long-term intervention trials. These provide a strong evidence base for recommending person specific targets for HbA1c, blood pressure and lipids. However, as diabetes specialists we also have an important role in ensuring that the condition is well managed during hospital admission and in this area there is very limited evidence on which to base recommendations. The incidence of diabetes is rising exponentially and as a consequence the number of inpatients with diabetes is also rising. Attention is therefore focusing on inpatient care, with recognition that this is frequently suboptimal. The 2010 National Inpatient Audit reports a mean diabetes prevalence of 15% (range 6.6–24.3%) among inpatients in acute hospitals.1 The audit shows that patients with diabetes experience high levels of medication and management errors and increased length of stay.1,2 Guidelines for the management of inpatients with diabetes are needed to standardise and improve care across the UK. Surgery in people with diabetes is a neglected area, with surgeons and anaesthetists often happy with the idea of ‘permissive hyperglycaemia’, assuming that short (or even long) term hyperglycaemia is less likely to do the patient harm than a hypoglycaemic episode while under anaesthetic. However, recent data from the US have demonstrated that people with diabetes undergoing surgery have an almost 50% greater chance of postoperative mortality than those with normal glucose tolerance and have adverse consequences in all measures of postoperative morbidity.3 Furthermore, people with preoperative hyperglycaemia, who were not previously known to have diabetes, had a risk of perioperative death up to 12 times that of people without diabetes, rising to 40 times if the hyperglycaemia persisted postoperatively.3 These are powerful data and if you could tell your surgical colleagues that you could reduce their perioperative mortality by 12-fold without them even putting knife to skin, you would probably get their attention fairly swiftly. People with diabetes have voiced their concerns about the management of their diabetes while in hospital,4 and these are now being addressed. NHS Diabetes together with the Joint British Diabetes Societies (JBDS) produced excellent guidelines for the management of diabetic ketoacidosis and hypoglycaemia, and have commissioned guidelines for the perioperative management of diabetes.5 Over the last two years, a group comprising diabetes consultants, diabetes specialist nurses, anaesthetists and surgeons has been working on these guidelines to improve the standards of care for people with diabetes undergoing elective surgery or procedures requiring a period of starvation. This is a complex area, with sometimes conflicting views about the optimum management, depending on whether the focus is on the surgical procedure, anaesthesia or diabetes. Patient views have been taken into account and National Patient Safety Agency alerts about safe use of insulin have been incorporated. These guidelines were formally launched at Diabetes UK in March 2011. A summary: this details the seven stage patient journey with aims and an action plan for each stage.5 Appendices provide examples of recommendations for diabetes management at each stage. This document has been sent to all chief executives, medical directors, diabetes departments, and surgical and anaesthetic clinical governance leads to ensure widespread publicity. The main document: this is expanded to discuss the evidence for the recommendations and includes a section on controversial areas, where the evidence is either conflicting or lacking. The main document is not intended to be read from cover to cover, but is a resource for those writing local guidelines. This document is only available online at www.diabetes.nhs.uk/our_work_areas/inpatient_care/perioperative_management/. It is aimed at managers and local guideline writers to allow them to create a seamless pathway between primary and secondary care. There is sufficient flexibility within the guidelines to accommodate local variation but the overriding focus remains the care of the person with diabetes. At each stage of the patient pathway the responsibilities of the health care professionals are spelled out with the emphasis on communication. For example, at the primary care stage a minimum data set indicates the information that general practitioners should provide to the surgeons in the referral letter. The surgeon has responsibilities to ensure that the preoperative assessment clinic is aware that the patient has diabetes and to ensure that the patient is placed early on the list. The preoperative assessment clinic staff should ensure that a management plan is in place so that, when the person arrives for day-of-procedure admission, there are no surprises for patient or staff. One of the aims of the document is to prevent the almost wholly unnecessary practice of overnight pre-admission for ‘glycaemic optimisation’. As the Diabetes UK focus group observes, this often means taking the patient's insulin away from them, putting them on a variable rate intravenous insulin infusion (VRIII) and leaving them to be managed by junior surgical nursing staff on nights who are responsible for dozens of patients but have little or no knowledge of how to manage diabetes. The writing group acknowledges that substantial parts of the guidelines are not ‘evidence based’, because evidence is not available but, where there is evidence, this has been quoted. High blood glucose levels pre- and postoperatively have been shown to be associated with poor outcomes, but there is little evidence to show that strict perioperative glycaemic control is associated with good outcomes or to indicate what the glycaemic targets should be. Hence, the glycaemic targets are modest: an HbA1c of <69mmol/mol (8.5%) prior to referral, or a blood glucose of between 6 and 10mmol/L (4–12 is acceptable) during the in-patient stay. Controversial areas discussed in the main document include glycaemic targets and choice of intravenous fluids for use with a VRIII. Traditionally, 5% glucose has been the fluid of choice but there is evidence that this is associated with hyponatraemia.6-8 The fluid options are discussed in an appendix, but the recommended fluid is 0.45% sodium chloride with 5% glucose. Although this fluid is more costly than 5% glucose and less widely available, negotiations are ongoing to make it both cheaper and more accessible. The document is a dynamic one. There is no ‘one size fits all’ for all surgical units across the UK and the writing group strongly urges local providers to adapt the guidelines for their own use. Where there are differences in practice, units are encouraged to report their experience to the writing group. If units have evidence to show that their strategy for management of people with diabetes is safe, we encourage them to publish in order to expand the evidence base for the recommendations. There are no conflicts of interest declared.
In this cross-sectional study, we investigated the prevalence of hypertriglyceridaemia (hyperTG) in 182 statin-treated type 2 diabetic (T2DM) patients.Predictors of hyperTG (>= 2.3mmol/L) were investigated using logistic regression. The prevalence of hyperTG was 20.9%, with lower prevalence in patients with low-density lipoprotein (LDL)-cholesterol < 2.5mmol/L (13.7%), and LDL-cholesterol < 2.0mmol/L (8.8%). The prevalence of hyperTG plus low high-density lipoprotein (HDL)-cholesterol (<= 0.9mmol/L) was lower at 6.0%. The independent predictors of hyperTG were waist circumference (odds ratio [OR] 1.033 [95% confidence interval 1.004-1.063], p=0.027) and glucose (OR 1.30 [1.05-1.61], p=0.01), with glucose being the sole predictor in patients with LDL-cholesterol < 2.5mmol/L (OR 1.45 [1.11-1.89], p=0.01) and LDL-cholesterol < 2.0mmol/L (OR 1.59 [1.12-2.26], p=0.01).In this group of statin-treated T2DM patients, the prevalence of hyperTG was relatively high, but lower in patients with lower LDL-cholesterol levels. Residual hyperTG in statintreated patients could be addressed by therapeutic lifestyle interventions aimed at weight loss and improved glycaemic control and by further lowering of LDL-cholesterol. Copyright (C) 2011 John Wiley & Sons.
Nutrition labelling on foods can provide consumers with invaluable information on which to base important decisions affecting their health in a variety of ways. Indeed, it has long been promoted as an important information source by health professionals and, with the rise in the amount of convenience foods eaten, which invariably display a nutrition label, it could prove to be an increasingly significant area for health education. However, how many health professionals and patients truly understand food labels? Many readers will be surprised to learn there is currently no legal requirement in the UK or Europe to include nutrition information on food labels unless the product is making some form of nutritional claim. Likewise, for those manufacturers who decide to volunteer such information, there are no rules on exactly what they should provide and in what format (i.e. layout, position on the label, text size etc). It could be said therefore that nutrition labelling is somewhat of a minefield for the average consumer, let alone a person with diabetes. Studies have demonstrated that freedom to eat in diabetes has a major impact on quality of life for people with diabetes, over and above other aspects of their diabetes such as ‘worries about the future’.1 The article by Dr TA Deakin provides an informative background to the area of food labelling and diabetes and focuses on relatively simple measures that may help consumers to read and interpret nutrition labelling. The author supports calls for European uniformity in nutrition labelling, but in the meantime this small study using a structured questionnaire demonstrates there is value in offering consumers educational resources and a magnifying glass, particularly for older age groups. Cost implications for health services are not considered in the study; however, it would seem wise to target resources to those with the greatest need and potential benefit, and perhaps the food industry itself could provide financial support.
AbstractOur patient is a 40‐year‐old man with a 22‐year history of type 1 diabetes. His control had been consistently poor but he had minimal end organ damage. There was no significant past medical history or family history. He was a C1 driving licence holder, and the DVLA was aware of his diagnosis of type 1 diabetes.In January 2007 he unexpectedly lost 8kg in weight and found he required less insulin. He had frequent hypoglycaemic episodes, but did not seek medical attention.Five months later he was involved in a road traffic accident that was fatal to the other driver. The paramedics found him to be hypoglycaemic. This resulted in a custodial sentence, and lifetime driving ban.He was subsequently admitted to hospital to investigate his hypoglycaemia. Thyroid function and synacthen tests were normal. Coeliac serology was negative and he was mildly anaemic. His HbA1c was elevated at 10.4% (90mmol/mol). He was discharged without cause found.A month later he was readmitted with breathlessness. He was severely anaemic with an Hb of 7.8g/dl, and was referred for gastroscopy. This demonstrated hyperplastic gastritis of the stomach, with altered blood present. Duodenal biopsies were taken and showed subtotal villous atrophy with a patchy increase in intraepithelial lymphocytes and crypt hyperplasia. The findings were consistent with coeliac disease. The patient was referred to a dietitian for advice on a gluten‐free diet. His haemoglobin normalised and a DEXA scan excluded osteoporosis. Copyright © 2011 John Wiley & Sons.
AbstractHypoglycaemia unawareness can be a devastating complication in both types of diabetes. It is probably becoming more common as patients are urged to tighten their glycaemic control. The effects of improving glycaemic control on the background of increasing duration of diabetes are the main known risk factors for the condition. Antecedent hypoglycaemia diminishes physiological responses, and impairs the ability to identify further episodes, leading to a vicious downwards spiral and a high risk of further severe hypoglycaemic episodes. Fully established hypoglycaemia unawareness is thankfully rare, but difficulty in recognising the onset of hypoglycaemia is common. Therefore effective treatments to reverse or prevent hypoglycaemia unawareness are urgently needed.This review article examines the evidence around the pathophysiology of hypoglycaemia unawareness, and current therapeutic strategies. Copyright © 2011 John Wiley & Sons.
Diabetes UK has supported the concept of integrated diabetes care to ensure that the person with diabetes is seen by the right professional at the right time in the right place. At a time when diabetes teams are threatened by changes in the NHS, the division between mental and physical health services makes those with mental illness particularly vulnerable.The association between diabetes and mental illness has been recognised for over 350 years. The prevalence of diabetes in people with depression and severe mental illness (schizophrenia and bipolar illness) is increased two-to three-fold. Furthermore, the proportion of people with undiagnosed diabetes is considerably higher than in the general population. The risk of complications and diabetes related mortality is higher in those with co-morbid mental illness.Currently, diabetes services for people with severe mental illness lag behind those for people without mental illness; patients are less likely to be examined for eye or foot complications, less likely to be screened for glycated haemoglobin or cholesterol, and less likely to receive education.Integration of care between mental and physical health services, whether in primary or secondary care, is essential if this health inequality is to be overcome. Perhaps only then can we bring body, mind and soul back together. Copyright (C) 2011 John Wiley & Sons.
AbstractIt is a myth that screening of type 2 diabetes is ‘a given’, that we provide adequate education for patients and that increasing physical activity by simply referring patients to a health trainer can prevent type 2 diabetes. Research in this area is often seen as an easy or soft option. On closer inspection, research of these ‘complex’ interventions requires rigorously conducted and well designed trials which are difficult to do and even harder to implement. The process of screening for type 2 diabetes is feasible and a number of practice level and self‐assessment tools are effective in the multi‐ethnic UK population; however, providing the evidence of whether a screening programme will lead to improved patient outcomes is more challenging.Providing structured self‐management education in type 2 diabetes can be effective in both biomedical and psychological outcomes, but the role of the educators is key. Such programmes can be cost effective, and can be implemented on an industrial scale whilst maintaining consistency and quality. Increasing physical activity and reducing sedentary behaviour to prevent type 2 diabetes are possible in the UK, and tailored strategies for younger and black/minority ethnic groups are being developed. Copyright © 2011 John Wiley & Sons.
